EICOSANOID BIOSYNTHESIS DEFICIENCY
EICOSANOID BIOSYNTHESIS DEFICIENCY
批准号:
7605582
负责人:
JOHN Alexander OATES
金额:
$0.37万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2006
资助国家:
美国
项目状态:
已结题
起止时间:
2006-12-01 至 2007-09-16
关键词:
AnabolismBiochemicalCalciumCellsClinicalComplexComputer Retrieval of Information on Scientific Projects DatabaseDefectEicosanoidsEicosatetraenoic AcidsEnzymesFundingGenesGeneticGenotypeGrantGrowth Factor OncogenesHumanIndividualInstitutionKnowledgeLipoxygenaseMapsMeasuresMolecularMolecular GeneticsMutationPathway interactionsPatientsPhospholipase A2PhospholipidsPhosphorylationPlatelet aggregationProcessProstaglandin-Endoperoxide SynthaseProstaglandinsProtein AnalysisRegulationResearchResearch PersonnelResourcesRoleSerumSourceUnited States National Institutes of HealthWestern Blottingcyclooxygenase 1cyclooxygenase 2cytokineurinary
中文摘要
这个子项目是许多研究子项目中的一个
由NIH/NCRR资助的中心赠款提供的资源。子项目和
研究者(PI)可能从另一个NIH来源获得主要资金,
因此可以在其他CRISP条目中表示。所列机构为
研究中心,而研究中心不一定是研究者所在的机构。
主要假设:确定的患者具有胞质PLA 2酶的突变。
次要假设:确定的患者存在胞浆PLA 2调节机制缺陷。
我们已经确定了一个病人的多个测量显着低水平的三尖杉酯碱,环氧合酶途径的产品,和12-羟基-二十碳四烯酸(12-HETE),脂氧合酶途径的产品,这表明一个功能性PLA 2酶缺乏症。 我们试图进一步阐明这些生化缺陷的分子机制。 我们将首先定量血清和尿液中常见的环氧合酶和脂氧合酶途径的代谢产物,以及血小板聚集和磷脂表征的功能分析,以确认该个体的分子缺陷。 在确认酶缺乏后,我们将通过蛋白质的Western印迹分析来评估酶是否完全不存在于细胞中或以改变的形式存在。 然后,我们将在基因水平上进行描述。
人类PLA 2的调节涉及一个复杂的过程,包括钙释放调节的激活、磷酸化、易位和多种其他调节因子,如细胞因子、生长因子和癌基因。 由于人类胞质和分泌型PLA 2基因已被映射和功能结构域很好地描述,这些酶的基因分型将有助于查明我们的病人的功能缺陷的机制,并划定之间的缺陷PLA 2酶本身或调节机制。 在分子和遗传水平上定义该患者的缺陷将显著有助于了解PLA 2酶在人类中的作用及其抑制的临床后果。
英文摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Primary Hypothesis: The identified patient has a mutation of the cytosolic PLA2 enzyme.
Secondary Hypothesis: The identified patient has a defect in regulatory mechanism of cytosolic PLA2.
We have identified a patient with significantly low levels of multiple measured prostaglandins, products of the cyclooxygenase pathway, and 12-hydroxy-eicosatetraenoic acid (12-HETE), a product of the lipoxygenase pathway, suggesting a functional PLA2 enzymatic deficiency. We seek to further elucidate the molecular mechanism for these biochemical deficiencies. We will initially quantify serum and urinary metabolites of common cyclooxygenase and lipoxygenase pathways, in addition to functional analysis of platelet aggregation and phospholipid characterization to confirm the molecular defect in this individual. Following confirmation of the enzymatic deficiency, we will assess whether the enzyme is entirely absent from the cells or present in an altered form by performing Western blot analysis of the protein. We will then pursue description on a genetic level.
PLA2 regulation in humans involves a complex process including calcium release-regulated activation, phosphorylation, translocation, and multiple other modulatory factors such as cytokines, growth factors, and oncogenes. Because human cytosolic and secretory PLA2 genes have been mapped and functional domains well described, genotyping of these enzymes will assist in pinpointing the mechanism of functional deficiency in our patient and delineating between a defect in the PLA2 enzyme itself or in a regulating mechanism. Defining the deficiency in this patient on molecular and genetic levels will contribute significantly to the knowledge of the role of PLA2 enzymes in humans and clinical consequences of their inhibition.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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批准号:9248194
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项目类别:
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资助金额:$15.85万
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财政年份:2015
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负责人:JOHN Alexander OATES
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Prevention of genomic instability by a scavenger of bifunctional electrophiles
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资助金额:$20.4万
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财政年份:2015
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依托单位:
Prevention of COX-2 Derived DNA and Histone Modifications in Cancer
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批准号:9017969
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项目类别:
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资助金额:$1.43万
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财政年份:2015
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依托单位:
Development of Compounds for the Prevention and Treatment of Rhabdomyolysis
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批准号:8834621
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项目类别:
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资助金额:$37.41万
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财政年份:2014
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负责人:JOHN Alexander OATES
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依托单位:
Lipid Modification of Proteins by the PGH Synthases
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批准号:7929873
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项目类别:
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资助金额:$34.15万
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财政年份:2009
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负责人:JOHN Alexander OATES
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依托单位:
SCCOR in Hemostatic and Thrombotic Diseases
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批准号:7808876
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项目类别:
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资助金额:$339.22万
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财政年份:2006
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负责人:JOHN Alexander OATES
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依托单位:
SCCOR in Hemostatic and Thrombotic Diseases
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批准号:7622651
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项目类别:
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资助金额:$335.64万
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财政年份:2006
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负责人:JOHN Alexander OATES
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依托单位:
EICOSANOID BIOSYNTHESIS DEFICIENCY
-
批准号:7731407
-
项目类别:
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资助金额:$0.02万
-
财政年份:2006
-
负责人:JOHN Alexander OATES
-
依托单位:
THE PHARMACOLOGY OF ASPIRIN
-
批准号:7250527
-
项目类别:
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资助金额:$46.98万
-
财政年份:2006
-
负责人:JOHN Alexander OATES
-
依托单位:
THE PHARMACOLOGY OF INHIBITORS OF HEME PROTEIN-CATALYZED LIPID PEROXIDATION
-
批准号:7209628
-
项目类别:
-
资助金额:$23.48万
-
财政年份:2006
-
负责人:JOHN Alexander OATES
-
依托单位:
SCCOR in Hemostatic and Thrombotic Diseases
-
批准号:7408528
-
项目类别:
-
资助金额:$323.64万
-
财政年份:2006
-
负责人:JOHN Alexander OATES
-
依托单位:
LOSS OF EFFECT OF ASPIRIN
-
批准号:7731404
-
项目类别:
-
资助金额:$0.02万
-
财政年份:2006
-
负责人:JOHN Alexander OATES
-
依托单位:
LOSS OF EFFECT OF ASPIRIN
-
批准号:7605579
-
项目类别:
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资助金额:$0.42万
-
财政年份:2006
-
负责人:JOHN Alexander OATES
-
依托单位:
SCCOR in Hemostatic and Thrombotic Diseases
-
批准号:7234680
-
项目类别:
-
资助金额:$317.49万
-
财政年份:2006
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负责人:JOHN Alexander OATES
-
依托单位:
LOSS OF EFFECT OF ASPIRIN
-
批准号:7375658
-
项目类别:
-
资助金额:$3.1万
-
财政年份:2005
-
负责人:JOHN Alexander OATES
-
依托单位:
Lipid-Modification of Proteins in Alzheimer's Disease
-
批准号:6907071
-
项目类别:
-
资助金额:$18.67万
-
财政年份:2005
-
负责人:JOHN Alexander OATES
-
依托单位:
Lipid-Modification of Proteins in Alzheimer's Disease
-
批准号:7054770
-
项目类别:
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资助金额:$15.29万
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财政年份:2005
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负责人:JOHN Alexander OATES
-
依托单位:
LOSS OF EFFECT OF ASPIRIN
-
批准号:7207314
-
项目类别:
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资助金额:$0.78万
-
财政年份:2004
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负责人:JOHN Alexander OATES
-
依托单位:
EICOSANOID BIOSYNTHESIS DEFICIENCY
-
批准号:7207316
-
项目类别:
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资助金额:$0.97万
-
财政年份:2004
-
负责人:JOHN Alexander OATES
-
依托单位:
PARTICIPATION OF CYCLOOXYGENASE-2 OVERPRODUCTION OF PROSTAGLANDIN D2 IN PATIENT
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批准号:7207197
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项目类别:
-
资助金额:$0.74万
-
财政年份:2004
-
负责人:JOHN Alexander OATES
-
依托单位:
海外基金